Understanding the neurobiology of memory consolidation is crucial to the development of treatments for memory-related disorders, such as post-traumatic stress disorder and phobias. Considerable evidence indicates that the basolateral amygdala (BLA) interacts with a variety of forebrain structures to influence the consolidation for different types of learning, but previous work has been unable to examine the roles of specific pathways from the BLA in the memory consolidation for distinct types of learning. The recent development of optogenetics now enables optical control over structures, as well as their projections to efferent regions, with excellent temporal and spatial precision. Th long-term objective of the proposed research is to use optogenetics to investigate the neural circuitry, and especially the projections connecting structures, during memory consolidation. The present R21 will develop the use of optogenetics in the study of memory consolidation as a foundation for future research investigating larger neural circuits. In the present experiments, the basolateral amygdala (BLA) will be virally transduced to express the depolarizing cation channel channelrhodopsin-2 (ChETA) or the hyperpolarizing outward proton pump archaerhodopsin-3 (ArchT). Because the opsins are expressed along the entire cell membrane, including the axons, illumination can also be provided to structures, such as the nucleus accumbens (NA), that receive BLA input to control that specific pathway. In the present experiments, rats will be trained in a modified contextual fear conditioning (CFC) task that separates the context learning from the footshock learning. Thus, the current proposal will use optogenetic control over the BLA and its projections to the NA to determine how these neural circuits influence consolidation for different kinds of learning. Aim 1 will investigate how optogenetic control of the BLA influences the consolidation of the footshock vs. context learning in the modified CFC task. In Aim 1, we will use a variety of different illumination parameters to stimulate (via ChETA expression) or inhibit (via ArchT expression) BLA activity immediately after training. Aim 1's findings will provide critical knowledge about how optogenetic control of BLA glutamatergic neuron activity influences memory consolidation. Aim 2 will examine how optical control over the BLA's projections to the NA (shell vs. core) influences the consolidation of context vs. footshock learning. Aim 2 will take advantage of the ability of optogenetics to control specific projection pathways by illuminating opsin-expressing BLA fibers in the NAshell or core. These findings will answer previously intractable questions about the pathways from the BLA to the NAshell and core during the consolidation of different aspects (context vs. footshock) of CFC learning. Together, these experiments will provide a critical foundation in the application of optogenetics to the understanding of the neural circuits involved in memory consolidation and answer major questions regarding the circuits from the BLA to the NA during consolidation for different types of learning. PUBLIC HEALTH RELEVANCE: Public health relevance: Disorders of emotionally influenced learning and memory, such as post-traumatic stress disorder and phobias, remain serious concerns in our society. The proposed research will investigate the neural circuitry modulating memory consolidation underlying such learning processes, laying the foundation for future research into treatments for memory disorders.